Association between plasma cytokine levels and multiple neuroimaging modalities in mild cognitive impairment

Background: The relationship between peripheral cytokines and neuroimaging biomarkers for Alzheimer's disease (AD) is not yet well established. Objective: To determine the association of cytokine plasma levels with brain amyloid deposition, cortical glucose metabolism, hippocampal volume, and white matter lesions (WMLs) in older adults with mild cognitive impairment (MCI). Methods: We recruited 50 older individuals with amnestic MCI (25 men and 25 women; median age, 75 years) and performed plasma analysis, C-11-Pittsburgh compound-B positron-emission tomography (PiB-PET), F-18-fluorodeoxyglucose positron-emission tomography, and magnetic resonance imaging. Global PiB and fluorodeoxyglucose (FDG) uptake were assessed by the ratio of the voxel number-weighted average of the mean uptake in the frontal, temporoparietal, and posterior cingulate, in reference to the cerebellum. The Fazekas scale was used to evaluate WMLs. Plasma levels of 48 cytokines were simultaneously measured with bead-based multiplex assays. Results: The plasma levels of IL-2Ra, IL-3, IL-5, IL-7, IL-9, IL-16, IL-18, fibroblast growth factor (FGF-basic), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein-1 alpha (MIP-1 alpha), regulated on activation, normal T-cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-alpha), cutaneous T-cell attracting chemokine (CTACK), growth-regulated oncogene alpha (GRO alpha), hepatocyte growth factor (HGF), interferon-alpha 2 (IFN-alpha 2), leukemia inhibitory factor (LIF), monocyte chemoattractant protein-3 (MCP-3), beta-nerve growth factor (beta-NGF), stem cell factor (SCF), stem cell growth factor-beta (SCGF-beta), and TNF-related apoptosis-inducing ligand (TRAIL) were significantly associated with global PiB uptake, whereas those of IL-7 and GRO alpha were significantly associated with hippocampal volume after covariate adjustment and false discovery rate correction. Conclusions: Plasma cytokines are associated with brain amyloid deposition rather than brain dysfunction or hippocampal atrophy. Moreover, cytokines may play important roles in early-stage AD pathophysiology.